Bevacizumab With or Without Docetaxel in Treating Patients With Previously Treated Metastatic Pancreatic Cancer

Phase II and Coagulation Study of rhuMAb-VEGF With or Without Docetaxel in Patients With Previously Treated Metastatic Pancreatic Adenocarcinoma

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining bevacizumab with docetaxel may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying bevacizumab and docetaxel to see how well they work compared to bevacizumab alone in treating patients with metastatic pancreatic cancer.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: docetaxel; Drug: rhuMAB-VEGF

Detailed Description

OBJECTIVES:

• Determine the progression-free survival of patients with previously treated metastatic pancreatic adenocarcinoma treated with bevacizumab with or without docetaxel.
• Determine the objective response rate and overall survival of patients treated with these regimens.
• Determine the incidence of thromboembolic events in patients treated with these regimens.

OUTLINE: This is a randomized, open-label study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and docetaxel IV over 1 hour on days 1, 8, and 15.
• Arm II: Patients receive bevacizumab as in arm I. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 46 patients (23 per treatment arm) will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Fox Chase Cancer Center - Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the pancreas

  • Metastatic disease

• Unidimensionally measurable disease outside of the pancreas

  • At least 1 lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
• Must have received 1, and only 1, prior gemcitabine-containing regimen for metastatic disease unless disease has recurred within 6 months after treatment with neoadjuvant or adjuvant gemcitabine-containing therapy
• No brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.0 g/dL (transfusion allowed)
• No bleeding diathesis or coagulopathy

Hepatic

• Bilirubin no greater than upper limit of normal (ULN)
• AST and ALT no greater than 1.5 times ULN
• INR no greater than ULN
• PTT no greater than ULN

Renal

• Creatinine no greater than 2.0 mg/dL
• No clinically significant renal impairment
• Urine protein:creatinine ratio ≥ 1.0

Cardiovascular

• No prior myocardial infarction
• No prior stroke
• No clinically significant cardiovascular disease
• No uncontrolled hypertension (i.e., blood pressure greater than 160/110 mm Hg on medication)
• No unstable angina
• No New York Heart Association class II-IV congestive heart failure
• No serious cardiac dysrhythmia requiring medication
• No peripheral vascular disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history or evidence of CNS disease (e.g, primary brain tumor or seizures not controlled with standard medical therapy)
• No other medical condition that would preclude study participation
• No psychiatric condition that would preclude study participation
• No other prior or concurrent malignancy that would preclude study participation
• No significant traumatic injury within the past 28 days
• No serious, nonhealing wound, ulcer, or bone fracture

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent prophylactic granulocyte or platelet growth factors

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• At least 4 weeks since prior radiotherapy

Surgery

• More than 7 days since prior fine needle aspirations or core biopsies
• More than 28 days since prior surgery (except closed biopsy or access port placement)
• More than 28 days since prior open biopsy
• No concurrent surgery

Other

• More than 4 weeks since prior experimental drug study participation
• More than 4 weeks since prior investigational drugs
• No other concurrent experimental drug study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rhuMAB-VEGF; bevacizumab 10 mg/kg by intravenous infusion over 30-90 minutes once every 2 weeks until disease progression, unacceptable toxicity or patient preference.	Drug: rhuMAB-VEGF
Experimental: rhuMAB-VEGF and Docetaxel; rhuMAB-VEGF,bevacizumab: 10 mg/kg by intravenous infusion over 30-90 minutes once every 2 weeks docetaxel, Taxotere: 35 mg/m2 given intravenously over 1 hour on days 1, 8, and 15 of each 28 day cycle. Treatment continued until evidence of disease progression, unacceptable toxicity, or patient preference.	Drug: docetaxel; Drug: rhuMAB-VEGF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free Survival	4 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate	56 days
Overall Survival	From date of registration until the date of death, assessed up to 5 years
Number of Participants With Thromboembolic Events	93 days

Collaborators and Investigators

• Sponsor: Fox Chase Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Steven J. Cohen, MD, Fox Chase Cancer Center

Publications and helpful links

General Publications

• Astsaturov IA, Meropol NJ, Alpaugh RK, Burtness BA, Cheng JD, McLaughlin S, Rogatko A, Xu Z, Watson JC, Weiner LM, Cohen SJ. Phase II and coagulation cascade biomarker study of bevacizumab with or without docetaxel in patients with previously treated metastatic pancreatic adenocarcinoma. Am J Clin Oncol. 2011 Feb;34(1):70-5. doi: 10.1097/COC.0b013e3181d2734a.

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: August 6, 2003
• First Submitted That Met QC Criteria: August 6, 2003
• First Posted (Estimate): August 7, 2003

Study Record Updates

• Last Update Posted (Actual): March 5, 2021
• Last Update Submitted That Met QC Criteria: February 15, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: recurrent pancreatic cancer; adenocarcinoma of the pancreas; stage IV pancreatic cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: CDR0000316454; P30CA006927 (U.S. NIH Grant/Contract); FCCC-03003